Beyond serial passages: new methods for predicting the emergence of resistance to novel antibiotics

Market launching of a new antibiotic requires knowing in advance its benefits and possible risks, and among them how rapidly resistance will emerge and spread among bacterial pathogens. This information is not only useful from a public health point of view, but also for pharmaceutical industry, in order to reduce potential waste of resources in the development of a compound that might be discontinued at the short term because of resistance development. Most assays currently used for predicting the emergence of resistance are based on culturing the target bacteria by serial passages in the presence of increasing concentrations of antibiotics. Whereas these assays may be valuable for identifying mutations that might cause resistance, they are not useful to establish how fast resistance might appear, neither to address the risk of spread of resistance genes by horizontal gene transfer. In this article, we review recent information pertinent for a more accurate prediction on the emergence and dispersal of antibiotic resistance.